Comparative efficacy of misoprostol and cimetidine in the treatment of acute duodenal ulcer. Results of major studies.

Misoprostol, a synthetic methyl ester of prostaglandin E1, has been shown to possess potent antisecretory activity in addition to a mucosal protective effect. Several multicenter double-blind, placebo-controlled trials confirmed the efficacy of misoprostol in the treatment of duodenal ulcer when administered at 800 micrograms in two or four divided doses daily. This report summarizes three cimetidine-controlled trials conducted in three separate geographic areas (Europe, Argentina, and Japan). The trials were double blind, randomized, and endoscopically controlled. In all studies, healing was defined as the absence of ulcer on endoscopy. The efficacy of misoprostol in the treatment of duodenal ulcer was shown to be equivalent to that of the histamine H2-receptor antagonist. In the Argentine study, the rate of disappearance of mucosal erosions was significantly greater for misoprostol than for cimetidine. Misoprostol was well tolerated. Mild and transient diarrhea not necessitating treatment or withdrawal occurred in 4 to 9 percent of the misoprostol-treated patients. These results indicate that misoprostol has a unique anti-ulcer action and represents a significant addition to the physician's armamentarium in the total medical management of duodenal ulcer.

[Effect of hydrochlorothiazide on acid secretion and potassium and sodium in the human gastric mucosa]. / Acción de la hidroclorotiazida sobre la secreción ácida, y el patasio y sodio de la mucosa gástrica humana.

Hydrochlorotiazide induced changes of gastric acid secretion, Sodium (Na) and potassium (K) of human gastric mucosa". In ten patients with elevated acid secretion we determined maximal acid secretion after histamine stimulation, Na and K in serum and in fundic mucosa obtained by peroral gastric biopsy. These experiments were performed before and after the oral administration of hydrochlorotiazide (200 mg/day) during seven days. After diuretic treatment we observed a significant decrease of Na (P less than 0.01) and K (p less than 0.05) in gastric mucosa. Both ions also decreased significantly in plasma (p less than 0.01). In gastric juice the decrease was significant for volume and peak acid output (p less than 0.01) and for total acidity (p less than 0.05). The significance of these findings is discussed.

[Plasma clearance of alpha 1-antitrypsin. A simple method for the study of intestinal protein loss]. / Depuración plasmática de alfa-1-antitripsina. Método simple para el estudio de la perdida proteica intestinal.

We tried to evaluate the value of the alpha-1-antitrypsin clearance in order to search for the protein loss through the digestive tract. Twenty-two patients were studied, 11 with protein losing enteropathy and 11 normal controls. Alpha-1-antitrypsin concentration was determined in serum and feces to obtain the clearance of such protein. The values were always abnormal in patients with protein losing enteropathy, and normal in control patients. We consider this method simple and safe for the evaluation of intestinal protein loss, besides having the advantage of not using radioactive material.

[Treatment of benign esophageal stenosis: re-evaluation after 20 years]. / Tratamiento de la estenosis benigna del esófago: re-evaluación a los 20 años.

In 1972 we described a method for dilatation of esophageal stenosis. The purpose of this paper is to report the results obtained between 1970 and 1989, the patients were studied by X-Rays, "calibration" of the stenosis, endoscopy, biopsy, cytology, gastric analysis and esophageal motility. One hundred and seven patients were treated (mean 60.5 years, M/F 3.9/1). The most frequent etiology was reflux esophagitis (80.3%). Hiatus hernia was present in 84.9%. The stenosis was in the lower third of the esophagus in 92.5%. The BAO was mean: 3.6 mEq/h, and the MAO mean 16.4 mEq/h with a hypersecretion pattern in 33.1% of the cases. Cytology was negative for malignancy in 100%. Biopsy showed esophagitis in 86.9%, Barrett's epithelium in 12.1%, normal tissue in 6.5% and insufficient material in 1.8%. Endoscopy showed 98.1% of grade IV esophagitis. Esophageal motility showed a HPZ of mean 6.5 mmHg. and varying degrees of aperistalsis in 24.3% of the patients. The total number of dilatations was 555 (mean 5.1/pt). The "calibration" of the stenosis previous to the dilatation was mean 8.6 mm, and post dilatation mean 15.6 mm. The result of the procedure was good in 92.5%, regular in 2.8% and bad in 4.6%. The morbidity was 0.9% and the mortality 0.1%. There was relapse of the stenosis in 42% of the cases, the follow-up was mean 3.2 years. Twenty nine patients were submitted to surgery due to failure of the procedure with 68.1% of good results, morbidity of 9% and mortality of 9%. We conclude that this dilatation procedure offers excellent results with a very low morbi-mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of benign esophageal stenosis by prolonged dilatation: re-evaluation after 15 years]. / Tratamiento de la estenosis benigna del esófago por medio de la dilatación prolongada: re-evaluación a los quince años.

The purpose of this paper is to re-appraise the results of a method for slow continuous dilatation of benign esophageal stenosis comparing previous experience of a decade with that accumulated during the following five-year period. A total of 78 patients were dilated, the average age was 58.1 years, and the M/F dilated, the average age was 58.1 years, and the M/F ratio 3.3/1. Reflux esophagitis was the most frequent etiology when comparing both groups (77.5% and 79.4% respectively). Esophageal hiatus hernia was the most common associated pathology in both groups (83.3% and 87.7% respectively). Gastric analysis showed average values within the limits of normal, 40% of de cases showed a hypersecretion pattern. The mean lower esophageal sphincter pressure was low, and a group of patients showed aperistalsis in more than 50% of the swallows, fact that was thought to be due to esophageal inability to clear the refluxed material. Another important fact was an increase in the frequency of Barrett's epithelium (6.5% to 9.3%). Undoubtedly the most important features were the increase in the number of good results of dilatation (87.7% to 92.3%), the decrease of morbidity (6.1% to 0.7%) and mortality (2% to 0.2%). The follow-up increased from X 27.3 to X 33.8 months.(ABSTRACT TRUNCATED AT 250 WORDS)

[Esophageal achalasia: review of the results after 15 years' experience]. / Acalasia del esófago: revisión de resultados a los quince años de experiencia.

The purpose of this paper is to evaluate the experience acquired along a 15 years period (1971-1985) in the treatment of achalasia of the esophagus. One hundred and fifty six patients were evaluated. The average age was 50.8 years, and the M/F ratio 0.9/1. Dysphagia was present in 100%, regurgitation in 78.2%, weight loss in 61.5%, and chest pain in 50% of the cases, being the main symptoms. Serology for Chagas disease was positive in 21.2% of the patients. When classified by radiologic criteria the groups were: grate I 18.5%, grate II 53.8%, grate III 14.7% and grate IV 12.8%. The high pressure zone was X 23 mmHg (N 14.8 mmHg) pre dilatation. The incidence of vigorous achalasia was 5.7% and the urecholine test was positive in 61.1%. Only 95 patients were submitted to pneumatic dilatation, and this is the group that we shall analyze in detail. We performed 110 dilatations, since 80 patients were dilated once and 15 received 2 dilatations. The high pressure zone post dilatations was X 12.5 mmHg. We obtained good results in 82.1%, regular in 3.1% and bad results in 14.7% of the patients. The morbidity was 4.5% (3 perforations and 2 gastroesophageal reflux), and the mortality 0.9%. There was relapse in 26.3% of the cases. In 53.3% of the patients submitted to a second dilatation we obtained good results. The average hospital stay was 2.5 days, and the follow up X 32.4 months. Thirty nine patients were sent to surgery with good results in 82%, regular in 2.5%, and bad in 15.6%. The morbidity was 15.3% and the mortality 5.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

[Megaesophagus secondary to carcinoma of the cardia: apropos of 4 cases]. / Megaesófago secundario a carcinoma de cardias: a propósito de 4 casos.

Four cases of megaesophagus with esophageal motor disturbances secondary to adenocarcinoma of the cardia are hereby reported. There were common characteristics to all cases such as: 1) short duration of symptoms, 2) grade II megaesophagus by X-Rays with narrowing of the cardia, 3) the endoscopy showed esophageal dilatation and inability to pass the cardia with the endoscope, 4) histology (obtained by endoscopy or surgery) and exfoliative cytology were positive for malignancy, 5) the esophageal motility tests showed aperistalsis of the whole esophagus in all cases, and lack of relaxation of the lower esophageal sphincter in two. The urecholine test was positive in one patient with neoplastic infiltration of the myenteric plexus, 6) in two cases where esophageal resection was performed, infiltration of the Auerbach's plexus by cancer cells was proven. We conclude that in the presence of aperistalsis of the esophagus with or without achalasia of the lower esophageal sphincter, the diagnosis of megaesophagus secondary to cancer of the gastric fundus should be suspected when it is not possible to pass the cardia with the endoscope, even if biopsy and cytology are negative for malignancy.

[Esophageal achalasia: 20 years' experience with non surgical treatment]. / Acalasia del esófago: veinte años de experiencia en el tratamiento no quirúrgico.

The purpose of this paper is to report the experience acquired in pneumatic dilatation in achalasia of the esophagus up to 1990. Two hundred and six patients were studied in that period (X 50, 7 years, M/F 1:1). According to X Rays the distribution was: grade I 17.4%, grade II 54.8%, grade III 14% and grade IV 13.5%. The associated esophageal pathology was: hiatus hernia 9.7%, esophagitis 5.8%, benign stenosis 2.4%, cancer 1.4%, ulcer and diverticula 0.9% and Schatzki's ring and leiomyoma 0.4% respectively Serology for Chagas disease was positive in 23% Chagasic megacolon was more frequent than chagasic heart disease (4.3% Vs. 1.4%). Out of these, one hundred and twenty patients were treated by pneumatic dilatation. To this group we shall refer in more detail. One hundred ant two patients were dilated once and the remaining 18 twice. Esophageal manometry showed a vigorous pattern in 7.7%. The LES' pressure pre-treatment was 24.5 mm Hg and post-dilatation 13.7 mm Hg in 75.8% of the cases the result was good. The morbidity was 5% and the mortality 0.7%. Relapse was seen in 25.8% of the cases. The follow-up was X 38 months. We conclude that pneumatic dilatation is the election procedure in the treatment of achalasia since it offers good results with low morbimortality. Surgery is indicated after failure of 2 dilatations, in children, and association with esophageal neoplasms, hiatus hernia and esophageal diverticula.

[Cimetidine in the treatment of the active duodenal ulcer]. / Cimetidina en el tratamiento de la úlcera duodenal activa.

Thirty six patients with active duodenal ulcers were studied in this double blind work. 19 received placebo and 17 Cimetidine: 1 gr./day. The endoscopic control after 21 days, showed healing in 81,2% of the cases treated with Cimetidine and in 22,2% of those with placebo. After 42 days of continous treatment with Cimetidine the healing of duodenal ulcers was 82,3% against 50% with placebo; the difference being highly statestically significant; p less than 0.01. The symptoms improved with Cimetidine revealing less diurnal and nocturnal pain complete disappearance of nausea and vomit and a significant decreased ingestion of alkali tablets.

[Achalasia of the esophagus]. / Acalasia del esófago.

Thirty-two cases of achalasia of the esophagus are studied in retrospect. The evolution was carried on from different standpoints: clinical, radiological, endoscopic, and motility studies. Patients were treated by dilatation (either pneumatic or mercury bougies) or surgery. The result of treatment was evaluated from the clinical standpoint correlating it with the remaining studies in order to establish wether or not they were related.

[Benign stenosis of the esophagus]. / Estenosis benigna de esófago.

In the present study 39 patients with benign esphageal stenosis were studied (average age 59,9 years). The most common etiology was refux esofagitis, and the most common associated pathology was esophageal hiatus hernia. Thirty one patients received medical treatment (diet. antireflux drugs and dilatations.) Twenty four were dilated with the slow continuous method, six with metalic bougies. One patient was not dilated. Seven patients were not treated since the stenosis was due to extrinsec compression. One patient was surgically treated from the onset. Seventy percent of the patients had goods results with esophageal dilatation. We propose that patients with benign esophageal stenosis should be treated by the slow continuous dilatation method.

[Atypical chest pain: study by the hydrochloric acid provocation test]. / Dolor torácico atípico: estudio mediante la prueba de provocación del ácido clorhídrico.

Evaluation by means of gastroenterological and cardiological methods. The purpose of this paper was to study the origin of chest pain (CP) in patients with normal and pathological coronary arteries as characterized by coronary arteriogram (CA). Sixteen normal control individuals (X 27 years -7 females and 9 males) were studied by means of esophageal manometry (EM) with a 3 way catheter perfused by a low compliance capillary system. Twenty-one patients with chest pain were studied and divided according to coronary arteriogram in normal (NC) and pathological arteries (PC). They were simultaneously studied by means of EM, heart rate/pressure product (RPP), and 12 lead ECG monitoring. After a basal period they were given a Bernstein's provocative chest pain test, and after each of its stages we determined in a simultaneous fashion CP, EM, ECG and RPP. In 61.9% of the patients abnormal basal EM was found. It was characterized by increase in HPZ, duration, propagation velocity and pressure of the peristaltic waves: as well as an increase in the percentage of aperistaltic waves. In 14.2% of the patients the Hydrochloric provocative test was positive. The only statistically significant datum was the heart rate/RPP relationship. We conclude that in future studies it would be of interest to combine 24 hour monitoring EM and pH as well as a more sensitive provocation test such as edrophonium chloride.

[Esophageal pathology associated with achalasia]. / Patología esofágica asociada a la acalasia.

Out of 90 patients with esophageal achalasia seen during the last decade, we found associated esophageal pathology in 46,6% of the cases. The esophagitis occurred with a frequency of 26,6%, whereas esophageal hiatus hernia was found in 14,4%, benign esophageal stenosis in 5,5%, diverticula in 2,2% and tumors in 2,2%. The role of the different ethiopatogeneic factors is discussed as well as the approach to the above mentioned entities.

[Action of metoclopramide bromide and metoclopramide chloride on the lower esophagogastric junction and the peristalsis of the lower 3d of the esophagus]. / Acción del bromuro de metoclopramida y del chlorhidrato de metoclopramida sobre el esfínter esofágico inferior y la peristalsis del tercio inferior del esófago.

In 10 patients with esophageal hiatus hernia the effect of metoclopramide bromide and metoclopramide chloride compared with placebo, was studied by the double blind method. Both drugs produced an increase of the lower esophageal sphincter pressure and of the peristalsis of the lower third of the esophagus, only being statistically significative the action of metoclopramide chloride on the perstalsis. No significative side-effects were noted.

[A double-blind study with misoprostol in the treatment of active duodenal ulcer]. / Estudio doble ciego con misoprostol en el tratamiento de la úlcera duodenal activa.

Misoprostol (Mi, a double blind study in the treatment of active duodenal ulcer (DU). The purpose of the paper was to evaluate the effect of Mi vs. Placebo (Pl) without antacids, assessing at the same time side effects and histological alterations. Thirty five patients with active DU diagnosed by endoscopy and photography (performed on days, 0, 14 and 28) were studied. They received 4 doses/day of Mi 100 mcg, or Pl double blind. In each control, biochemical studies in blood and urine were performed. Acetaminophen, 500 mg was the only analgesic allowed. Six patients were excluded. Of the remaining 29 patients, 15 received Mi and 14 Pl. There was no difference in healing at the 14 day stage. At the 28 day stage there was complete healing of the ulcer in 66.6%, and reduction of the ulcer diameter of 89% those who received Mi. The healing rate was 28.5% and reduction of the ulcer diameter of 31% on those patients who received placebo. There were no biochemical alterations or side effects. There was no significative difference between biopsies taken from pylorus and antrum. The consumption of acetaminophen was similar to both groups. It is concluded that Mi has a healing effect similar to H2 blocking agents, accelerating the healing of active DU, without side effects and biochemical changes.

[Gastroduodenal lesions in rheumatoid arthritis. Evaluation and treatment]. / Lesiones gastroduodenales en artritis reumatoidea. Evaluación y tratamiento.

In a group of 70 patients of both sexes been treated with antiinflammatory drugs, affected by Rheumatoid Arthritis in activity, we have found the presence of lesions, erosions and gastroduodenal ulcers in 40% by endoscopic examination (26% erosions and 14% ulcers), without any relation with clinical symptoms. Those patients who received larger doses than 30mgr./kg./day of AAS suffered most frequently lesions (43.8%). These 28 patients with lesions have been studied prospectively in a double blind method, and treated twice a day with 150 mgs. doses of Ranitidine or Placebo, throughout a period of 5 weeks without discontinuing the treatment with anti-inflammatories (AAS, Indomethacin, steroids). At the end of the trial those patients who failed in healing their lesions were treated with Ranitidine in the same doses for another period of 5 weeks. The treatment with Ranitidine in doses of 300 mgr/day has resulted curative of the gastroduodenal lesions, although maintaining the aggressive drugs, in the 87% of the patients. We have observed that the treatment with Placebo is less effective and that difference has high statistical significance (p 0.005).

[Misoprostol and cimetidine in the treatment of active duodenal ulcer. Multicenter, double-blind, clinico-endoscopic study. The Argentine experience]. / Misoprostol y cimetidina en el tratamiento de la úlcera duodenal activa. Estudio clínico-endoscópico, multicéntrico, doble ciego. Experiencia Argentina.

Ten Argentine centers participated in this cooperative trial. One hundred and sixteen patients with endoscopically proven duodenal ulcer entered the study and were randomly assigned to receive either Misoprostol 800 micrograms or Cimetidine 1200 mg, q.i.d. per day, during four weeks of treatment. Patients were allowed to take Amphogel tablets for relief of ulcer pain when necessary, and clinical, lab-tests and adverse effects were evaluated weekly. Ninety-nine patients (Misoprostol 54, Cimetidine 45) completed the study and were evaluable. Success/failure criteria were based on endoscopically documented complete healing at the end of treatment period. Healing rate of four week was 85.2 per cent (46/54) for Misoprostol and 75.5 per cent (34/45) for Cimetidine, with no statistically significant difference. It is concluded that Misoprostol and Cimetidine are highly effective and safety in the healing of active duodenal ulcer. Misoprostol is a new therapeutical alternative for the treatment of duodenal ulcer patients.